Tobacco use is estimated to be responsible for over 5 million deaths globally every year and HIV/AIDS kills 2 million worldwide, with persons living in the developing world especially at risk. However, the association between tobacco use and HIV is not clearly understood. The introduction of highly active antiretroviral therapy (HAART) has led to longer duration of survival following HIV-infection in the developed world, and now that HAART is being rolled out in the developing world, survival will increase in these highly endemic regions as well. Given this increase in survival, more people will die of non-HIV related illnesses for which smoking plays an important causal role. Smoking cessation for HIV-infected persons has been studied in the US though these studies have had small numbers and limited follow-up. US based studies suggest that approaches that combine nicotine replacement therapy (NRT) and counseling interventions are most successful. Optimal approaches in resource-limited settings have not been determined. The overall objective of this proposal is to conduct a randomized controlled trial (RCT) of intensive anti-smoking counseling plus nicotine replacement therapy (NRT) versus intensive anti-smoking counseling alone among HIV-infected patients in South Africa, and to concurrently measure the prevalence of smoking among HIV-infected patients in South Africa. We will compare NRT plus intensive anti-smoking counseling versus anti-smoking counseling alone, comparing smoking cessation at 2, 6 and 12 months. At 6 months, patients in the anti-smoking counseling arm will have the option to receive another round of their group assigned intervention. We will relate smoking exposure and cessation to HIV progression as measured by immunologic and viral markers, risk of respiratory infections, including tuberculosis (TB), and AIDS-related malignancies. The RCT will be performed at the Tshepong HIV Wellness Clinic in Klerksdorp, South Africa, associated with the University of the Witwatersrand, South Africa. Over 4,000 HIV- infected patients are seen monthly at this rural clinic. HIV prevalence in this region is high (19%) and an estimated 50% of the male HIV population smokes tobacco. This population is representative of the South African HIV population initiating HAART, and findings will be highly generalizable. Our primary focus on comparing two cessation strategies that are available to PWLHA in South Africa, but rarely utilized due to limited access, will provide comprehensive data towards understanding the effectiveness of these strategies. These findings will guide development of effective smoking cessation strategies in a region with high prevalences of HIV/AIDS and tobacco exposure. PUBLIC HEALTH RELEVANCE: This project is relevant to public health because information from the project will provide evidence to better understand the effectiveness of smoking cessation strategies among PLWHA in South Africa. Our primary focus on comparing two cessation strategies that are available to PWLHA in South Africa, but rarely used because of financial and access reasons, will provide comprehensive data towards understanding the effectiveness of these strategies. These findings will guide development of effective smoking cessation strategies in a region with high prevalences of HIV/AIDS and tobacco exposure.